Cardiac Toxicity

Hodgkin lymphoma survivors exposed to doxorubicin or thoracic radiation therapy are at risk of long-term cardiac toxicity. The effects of thoracic radiation therapy are difficult to separate from those of anthracyclines because few children undergo thoracic radiation therapy without the use of anthracyclines. The pathogenesis of injury differs, however, with radiation primarily affecting the fine vasculature of the heart and anthracyclines directly damaging myocytes.[26-28]

Survivors of childhood Hodgkin lymphoma older than 50 years experience more than two times the number of chronic cardiovascular conditions and nearly five times the number of more severe (grades 3–5) cardiovascular conditions compared with community controls. Also, survivors have one severe, life-threatening, or fatal cardiovascular condition, on average.[29]

Cardiac mortality is higher for survivors of adolescent Hodgkin lymphoma than for survivors of young adult Hodgkin lymphoma. This finding was demonstrated in the Teenage and Young Adult Cancer Survivor Study cohort, with standardized mortality ratios (SMR) of 10.4 (95% CI, 8.1–13.3) for those diagnosed at age 15 and 19 years, compared with an SMR of 2.8 (95% CI, 2.3–3.4) for those diagnosed at age 35 to 39 years.[30]

Applying a model to predict late cardiac toxic effects of therapy, patients with intermediate- and high-risk Hodgkin lymphoma who were treated in four consecutive COG trials between 2002 and 2020 were assessed for risk of grade 3 to grade 5 cardiac disease at 30 years after completion of therapy. Over this time period, the percentage of patients who received mediastinal radiation therapy decreased from 50% to less than 1%, which led to lower cardiac radiation exposure. Anthracycline doses increased from 200 mg/m2 to 300 mg/m2. However, use of the cardioprotectant dexrazoxane increased from 0% to 80%. The results demonstrated the predicted risk of grade 3 to grade 5 cardiac disease at 30 years will decrease from 10% to 6%, which would be highly statistically significant. The 6% incidence of cardiac disease is similar to the predicted 5% incidence for the general population, which questions the necessity of current long-term cardiac monitoring guidelines.[31]